the nih human microbiome project: catalyst for an emerging
TRANSCRIPT
The NIH Human Microbiome Project:Catalyst for an Emerging Field
Lita M. Proctor, Ph.D.Coordinator, Human Microbiome Project
National Human Genome Research Institute, NIH
(+ the work of thousands of scientists in US and abroad)
CHE webinarMay 24, 2016
1
2
Topics in this talk
1) Impetus for and goals of the HMP
2) Early findings about the human microbiome
3) Microbiome research beyond the HMP
4) National Microbiome Initiative
Society’s war against infectious disease(bubonic plague, smallpox, scarlet fever, yellow fever, tuberculosis, malaria,diptheria, dysentery, leprosy, typhoid fever…)
The MAJORITY (>> 99%) of microbes (bacteria,viruses, fungi) do not cause disease; many arebeneficial. Microbes on Earth:
► Soil production/regeneration► Oxygen production► Base of food webs (ocean, forests, etc)► Support plant, animal & human health
~1400 species of human pathogens
vs.
~1 - 10 million microbial species on Earth
Demonstration ProjectsHealthy cohort study
Human Microbiome Project, Phase One: a community resource(http://commonfund.nih.gov/hmp)
Phase 1 ($181M): Survey of the microbiome in humans
“Who’s there?”
Clinically healthy
300 male/female
18-40 y.o.
5 major body regions(18 body sites)
Up to 3 visits in 2 yrs
No antibiotics, probiotics,immunomodulators
Microbiome-associatedconditions
Skin: eczema, psoriasis, acne
GI/oral: esophagealadenocarcinoma, necrotizingenterocolitis, pediatric IBS,ulcerative colitis, Crohn’sDisease
Urogenital: bacterial vaginosis,circumcision, sexual histories
case:control
Human Microbiome Project, Phase Two: a community resource(http://hmp2.org)
Phase 2 (to date, ~$35M): Integrative HMP “iHMP”
“What are they doing?”
Analyse biological properties of both microbiome & hostover time to look for biomarkers of health and disease.
Three “model” microbiome-associated conditions:
longitudinal studies
Microbiota acquired anew each generation.Do
min
guez
-Bel
loet
al.(
2010
).
1) Infants obtain inoculum frommother or environment.
2) Microbial succession over~1-2 yrs.
3) Microbiome becomes“adult-like” in ~1-2 yrs.
Palm
eret
al.(
2007
)
Koen
iget
al.(
2010
)
Development of the immune system
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newborn three month old one year old six years old
Maternally-acquired (passive) immunityAdaptive immunity
Maternalimmunepropertiestransferredin utero.
Infant beginsproducingantibodies.
Antibodies at 15-20% of adult levels.
Normal antibodylevels.
Sources of microbes to the newborn, infant and child
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Uterus Breastmilk, food Food
Amniotic fluid Family members Other humans
Vagina Pets/animals
Breastmilk
Skin
Environment …………………… Environment ……………………… Environment
newborn three month old one year old six years old
We co-evolved with our microbiome:Immune system cannot mature without specific microbes.
Some bacteriainduce host
pro-inflammatory
response toprotect against
infection.
Others bacteriainduce hostanti-inflammatoryresponse torestore immunesystem balance.
Cross section of gut epithelium and bacterial community.(blue = gut wall cells green = mucous layer yellow and fuschia = bacteria)
micrograph from Earle et al. (2015)
gut wall cells
mucus layer
gut microbes (mostly bacteria)
Each of us host ~4000 bacterial species,which include ~4,000,000 bacterial genes.
Human genome? 20,000-23,000 genes
100-200x morebacterial genesthan human genesin humanecosystem.
Scientific American (2012)
Microbiota and host interact to regulatehuman health.
ü ‘educates’ the immune system torecognize self from nonself,
ü digests the ‘indigestables’(ex. plant material, host cells, mucus),
ü produces energy substrates forhost cells (ex. SCFAs),
ü metabolizes drugs,
ü produces beneficial compounds(ex. vitamins, antimicrobials)
ü produces signaling molecules whichcommunicate with the host,
ü gut microbiota communicate with thebrain
Though the human microbiome is a fixed feature,it is also a variable trait.
ü Between generationsü Throughout our lifetimesü Between health and disease
Unlike the human genome, the microbiome is naturally mutable.
Gut: irritable boweldisease (IBD),ulcerative colitis,Crohn’s disease,GERD, necrotizingenterocolitis (NEC)
Skin: eczema,psoriasis, acne
Heart:cardiovasculardiseases
Liver: non-alcoholicliver disease(NAFLD), alcoholicsteatosis
Cancers: esophageal cancer, colorectalcancer, Hodgkin’s lymphoma, cervicalcancer, liver cancer, gastric cancer
Lung: asthma,cystic fibrosis
Systemic: obesity, metabolic syndrome,rheumatoid arthritis, multiple sclerosis,autism, type 1 diabetes, type 2 diabetes
Brain/behavior: general brain function,epilepsy, Alzheimer’s, psychiatric disorders
The list of potential microbiome-associateddiseases/disorders is growing….
Vagina: bacterialvaginosis, pretermbirth
Atmosphericmicrobiomes
Soil & plantmicrobiomes
Astronaut/ISS microbiomes
Livestock/poultry microbiomes
Warfightermicrobiomes
Coral reef & oceanicmicrobiomes
Hospital & builtenvironmentmicrobiomes
Total Microbiome Research Funding FY12-14 byAgencyTotal Funding
for FY12-14:$921,786,776
USDA 4%
DOE 15%
NASA 3%DOD 4%
NIH56%
FDA 2%
USAID, CDC, Smithsonian, <1%
DOI 1%NSF 11%
NIST, $225,000 (0.02%)
NOAA <1%
EPA 1%
FTAC-MM2015
FTAC-MM:ü OSTP charterü FY12-14 data callü microbiome ‘writ large’ü 6 Departments (16 agencies), 4
Independent Agencies, 1 quasi-governmental entity
Data call results:ü $922M over FY12-14ü NIH comprised 56% of this totalü NSF and DOE comprised an
additional 26% of this total
Nature Microbiology paper:
$922M
FastTrack Action Committee – Mapping the Microbiome(FTAC-MM)
http
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http://dx.doi.org/10.1038/nmicrobiol.2015.15
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Microbiome research comes of age:The National Microbiome Initiative
https://www.whitehouse.gov/blog/2016/05/13/announcing-national-microbiome-initiative